Atherosclerosis is an inflammatory disease in which fatty material collects along the walls of arteries. Lusis, Nature, 407:233-241 (2000).
Urokinase-type plasminogen activator (uPA) promotes inflammatory cell adhesion and migration through binding to urokinase plasminogen activator receptor (uPAR). Gu et al., J. Cell Physiol., 204(1):73-82. uPA over-expressed by macrophages accumulates at atherosclerotic lesions, resulting in accelerated atherosclerosis. Cozen et al., Circulation, 109(17):2129-35 (2004). uPA receptor (uPAR) promotes macrophage infiltration into vascular walls in ApoE deficient mice, which is a mouse model for atherosclerosis. Gu et al., J. Cell Physiol., 204(1):73-82 (2005). Although all these results indicate that uPA/uPAR might play a role in the development of atherosclerosis, genetic depletion of uPA did not affect the formation of atherosclerotic lesions in ApoE deficient mice. Carmeliet et al., Nat. Genet., 17(4):439-44 (1997); Deng et al., Circ Res., 92(5):510-517 (2003).
The amino terminal fragment (ATF) of uPA is responsible for binding to uPAR. Both ATF and anti-ATF antibodies have been reported to be effective in treating cancer. Li et al., Hum. Gene Ther., 16(10):1157-67; Mazar et al., U.S. Patent Application 2005/0232924.